We are employing rat liver induced to regenerate by means of partial hepatectomy as a model for investigating growth regulation in mammalian cells. Hepatic regeneration is greatly delayed and diminished in rats surgically deprived of portal splanchic viscera, but is restored to normal (in terms of 3H-thymidine labeling of DNA) by simultaneous infusion of insulin and glucagon. Although not primary initiators of liver growth, these two hormones strikingly influence the liver when acting in synergy. Seeking further clarification of these results, we are currently investigating endogenous levels of pancreatic hormones in the portal vein in relation to liver cell proliferation under various experimental conditions in vivo. Likewise, we will examine their interactions with other hormones and putative growth regulatory factors. As a second exerimental model in which a liver deficit is created by non-surgical means (in collaboration with Drs. J.R. Wands and K.J. Isselbacher) we are studying the effects of insulin and glucagon upon fulminant hepatitis in mice heavily infected with A-59 murine hepatitis virus. All of the mice die with massive, acute liver necrosis. The two hormones together, but not separately, greatly enhance survival, again demonstrating synergy. We are probing possible mechanisms, both in vivo and in vitro. BIBLIOGRAPHIC REFERENCES: Farivar, M., Wands, J.R., Isselbacher, K.J., and Bucher, N.L.R.: Beneficial effects of insulin and glucagon on fulminant murine hepatitis. Gastroenterology 70:A123/981, 1976 (Abstract). Bucher, N.L.R.: Synergism of insulin and glucogen in regulating liver growth. J. Cell. Biology 70:282a, 1976 (Abstract).